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Identification of senescence-related molecular subtypes and key genes for prostate cancer

Asian Journal of Andrology 2023年第2期25卷 223-229页

作者： De-Chao Feng Wei-Zhen Zhu Xu Shi Qiao Xiong Jia You Qiang Wei Lu Yang Department of Urology Institute of UrologyWest China HospitalSichuan UniversityChengdu 610041China

We identified distinct senescence-related molecular subtypes and critical genes among prostate cancer(PCa)patients undergoing radical prostatectomy(RP)or radical radiotherapy(RT).We conducted all analyses using R software and its suitable *** genes,namely,secreted frizzled-related protein 4(SFRP4),DNA topoisomerase II alpha(TOP2A),pleiotrophin(PTN),family with sequence similarity 107 member A(FAM107A),C-X-C motif chemokine ligand 14(CXCL14),prostate androgen-regulated mucin-like protein 1(PARM1),leucine zipper protein 2(LUZP2),cluster of differentiation 38(CD38),cartilage oligomeric matrix protein(COMP),vestigial-like family member 3(VGLL3),apolipoprotein E(APOE),and aldehyde dehydrogenase 2 family member(ALDH2),were eventually used to subtype PCa patients from The Cancer Genome Atlas(TCGA)database and GSE116918,and the molecular subtypes showed good correlations with clinical *** terms of the tumor immune environment(TME)analysis,compared with cluster 1,cancer-associated fibroblasts(CAFs)scored significantly higher,while endothelial cells scored lower in cluster 2 in TCGA *** was a statistically significant correlation between both CAFs and endothelial cells with biochemical recurrence(BCR)-free survival for PCa patients undergoing *** the GSE116918 database,cluster 2 had significantly lower levels of CAFs and tumor purity and higher levels of stromal,immune,and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data(ESTIMATE)scores than cluster 1;in addition,patients with high levels of CAFs,stromal scores,immune scores,and ESTIMATE scores and low levels of tumor purity tended to suffer from *** on the median of differentially expressed checkpoints,high expression of CD96,hepatitis A virus cellular receptor 2(HAVCR2),and neuropilin 1(NRP1)in GSE116918 and high expression of CD160 and tumor necrosis factor(ligand)superfamily member 18(TNFSF18)in TCGA database were associated with a significantl

关键词： cellular senescence immune checkpoints molecular subtypes prostate cancer tumor immune environment

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Clinical significance of molecular subtypes of gastrointestinal tract adenocarcinoma

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World Journal of Gastrointestinal Oncology 2022年第3期14卷 628-645页

作者： Ekaterina Olegovna Ignatova Evgenii Kozlov Maxim Ivanov Vladislav Mileyko Sofia Menshikova Henian Sun Mikhail Fedyanin Alexey Tryakin Ivan Stilidi Department of Second Chemotherapy Federal State Budgetary Institution“N.N.Blokhin National Medical Research Center of Oncology”of the Ministry of Health of the Russian FederationMoscow 115478MoscowRussia Department of Oncogenetics Research Centre for Medical Genetics Research Centre for Medical GeneticsMoscow 115522MoscowRussia OncoAtlas LLC Moscow 121069MoscowRussia Department of Biological and Medical Physics Moscow Institute of Physics and TechnologyMoscow 141700MoscowRussia Department of Anticancer Drug Treatment AO K31 CityMoscow 121552MoscowRussia Pirogov Russian National Research Medical University(Pirogov Medical University) Moscow 117997MoscowRussia

Adenocarcinomas of the gastrointestinal tract(esophagus,stomach,and colon)represent a heterogeneous group of diseases with distinct etiology,clinical features,treatment approaches,and *** are ongoing to isolate molecular genetic subtypes,perform complete biological characterization of the tumor,determine prognostic groups,and find predictive markers to the effectiveness of *** molecular genetic classifications were created for esophageal adenocarcinoma[The Cancer Genome Atlas(TCGA)],stomach cancer(TCGA,Asian Cancer Research Group),and colon cancer(Colorectal Cancer Subtyping Consortium).In 2018,isolation of TCGA molecular genetic subtypes for adenocarcinomas of the gastrointestinal tract(esophagus,stomach,and colon)highlighted the need for further studies and clinical validation of subtyping of gastrointestinal ***,this approach has *** aim of our work was to critically analyze integration of molecular genetic subtyping of gastrointestinal adenocarcinomas in clinical practice.

关键词： Esophageal adenocarcinoma Gastric cancer Colon cancer Gene sequencing,Gene expression profiling molecular subtypes

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Signature based on molecular subtypes of deoxyribonucleic acid methylation predicts overall survival in gastric cancer

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World Journal of Gastroenterology 2020年第41期26卷 6414-6430页

作者： Jin Bian Jun-Yu Long Xu Yang Xiao-Bo Yang Yi-Yao Xu Xin Lu Xin-Ting Sang Hai-Tao Zhao Department of Liver Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

BACKGROUND Gastric cancer(GC) ranks as the third leading cause of cancer-related death worldwide. Epigenetic alterations contribute to tumor heterogeneity in early *** To identify the specific deoxyribonucleic acid(DNA) methylation sites that influence the prognosis of GC patients and explore the prognostic value of a model based on subtypes of DNA *** Patients were randomly classified into training and test sets. Prognostic DNA methylation sites were identified by integrating DNA methylation profiles and clinical data from The Cancer Genome Atlas GC cohort. In the training set, unsupervised consensus clustering was performed to identify distinct subgroups based on methylation status. A risk score model was built based on Kaplan-Meier, least absolute shrinkage and selector operation, and multivariate Cox regression analyses. A test set was used to validate this *** Three subgroups based on DNA methylation profiles in the training set were identified using 1061 methylation sites that were significantly associated with survival. These methylation subtypes reflected differences in T, N, and M category, age, stage, and prognosis. Forty-one methylation sites were screened as specific hyper-or hypomethylation sites for each specific subgroup. Enrichment analysis revealed that they were mainly involved in pathways related to carcinogenesis, tumor growth, and progression. Finally, two methylation sites were chosen to generate a prognostic model. The high-risk group showed a markedly poor prognosis compared to the low-risk group in both the training [hazard ratio(HR) = 2.24, 95% confidence interval(CI): 1.28-3.92, P < 0.001] and test(HR = 2.12, 95%CI: 1.19-3.78, P = 0.002) *** DNA methylation-based classification reflects the epigenetic heterogeneity of GC and may contribute to predicting prognosis and offer novel insights for individualized treatment of patients with GC.

关键词： Gastric cancer Deoxyribonucleic acid methylation molecular subtypes Prognosis Risk score The Cancer Genome Atlas

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MAT1 correlates with molecular subtypes and predicts poor survival in breast cancer

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Chinese Journal of Cancer Research 2018年第3期30卷 351-363页

作者： Hanxiao Xu Xianguang Bai Shengnan Yu Qian Liu Richard G Pestell Kongming Wu Department of Oncology Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Medical School of Pingdingshan University Pingdingshan 467000 China Pennsylvania Center for Cancer and Regenerative Medicine Wynnewood PA 19096 USA

Objective：Menage a trois 1（MAT1）is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA *** dysregulation is responsible for diseases including *** further explore the role of MAT1 in breast cancer,we investigated the pathways in which MAT1 might be involved,the association between MAT1 and molecular subtypes,and the role of MAT1 in clinical outcomes of breast cancer ***：We conducted immunohistochemistry staining on tissue microarray and immunofluorescence staining on sections of MAT1 stable breast cancer ***,we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis,correlation analysis and prognosis analysis on public ***：MAT1 was involved in multiple pathways including normal physiology signaling and disease-related ***,MAT1 positively correlated with the protein status of estrogen receptor and progesterone receptor,and was enriched in luminal-type and human epidermal growth factor receptor 2-enriched breast cancer in comparison with basal-like subtype at both m RNA and protein *** analysis revealed significant association between MAT1 m RNA amount and epithelial markers,mesenchymal markers,cancer stem cell markers,apoptosis markers,transcription markers and ***,the results of immunofluorescence stain indicated that MAT1 overexpression enhanced the protein abundance of epidermal growth factor receptor,vimentin,sex determining region Y-box 2 and sine oculis homeobox homolog ***,Kaplan-Meier Plotter analysis reflected that MAT1 could serve as a prognostic biomarker predicting worse relapse-free survival and metastasis-free ***：MAT1 is correlated with molecular subtypes and is associated with unfavorable prognosis for breast cancer patients.

关键词： Menage a trois 1(MAT1) breast cancer molecular subtypes prognosis proliferation

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Clinicopathological Features of Breast Cancer with Different molecular subtypes in Chinese Women

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2013年第1期33卷 117-121页

作者：程洪涛黄韬王伟岳君秋沈娜郭辉李大鹏赵群仔易鹏飞王瑞王龙强 Department of Breast and Thyroid Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Breast Surgery Hubei Cancer Hospital Department of Pathology Hubei Cancer Hospital

A retrospective study was performed to explore the relationship between molecular subtypes and clinicopathological features of breast cancer in Chinese women. Six hundred and twenty-eight Chi- nese women with breast cancer were classified into four molecular subtypes according to their estrogen receptor （ER）, progesterone receptor （PR） and Her-2 status. The prevalence rate of each molecular sub- type was analyzed. Relationship between the subtypes and clinicopathologic features was determined. The distribution of molecular subtypes was as follows： luminal A 46.5%, luminal B 17.0%, basal 21.5%, HER2/neu 15.0%. The subtypes had no significant difference under different menopausal status. How- ever, in the age-specific groups, the age group of〈35 years was more likely to get basal cell-like cancer （36.9%）. Statistically significant differences were found among molecular subtypes by age, nuclear grade, tumor size, lymph node （LN） metastasis, tumor stage by American Joint Committee on Cancer （AJCC）, radiotherapy but not by chemotherapy, types of surgery. After adjusting for several relative confounding factors, the basal subtype more likely had lower nodal involvement in both the incidence of LN metastasis （〉1 positive LN） and incidence of high-volume LN metastasis （〉4 positive LN）. The HER2/neu subtype had higher nodal involvement in the incidence of high-volume LN metastases. After adjusting for relative confounding factors, the HER2/neu subtype more likely had higher AJCC tumor stages. It was suggested that there existed close relationship between molecular subtypes and clinicopa- thological features of breast cancer. In addition, the breast cancer subtypes have been proven to be an independent predictor of LN involvement and AJCC tumor stage. These findings are very important for understanding the occurrence, development, prognosis and treatment of breast cancer in Chinese popu-lation.

关键词： breast cancer molecular subtypes clinicopathological features

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Magnetic Resonance Spectroscopy and Prognostic Analysis of molecular subtypes of Medulloblastoma

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Open Journal of Clinical Diagnostics 2020年第3期10卷 81-91页

作者： Yuting Zhang Lusheng Li Department of Radiology Children’s Hospital of Chongqing Medical University Chongqing China Department of Neurosurgery Children’s Hospital of Chongqing Medical University Chongqing China Ministry of Education Key Laboratory of Child Development and Disorders Chongqing China National Clinical Research Center for Child Health and Disorders Chongqing China Chongqing Key Laboratory of Pediatrics Chongqing China China International Science and Technology Cooperation Base of Child Development and Critical Disorders Chongqing China

Aim: The aim of this study was to investigate whether magnetic resonance spectrum (MRS) and MR imaging features can be used for non-invasive medulloblastoma subgrouping, and analyse patient characteristics and prognosis of molecular subtypes of medulloblastoma. Material and Methods: 32 patients with medulloblastoma underwent MRI prior to surgical resection, 16 of them underwent MRS. MR imaging features and metabolites measured by MRS were analysed to distinguish molecular subtypes of medulloblastoma. Patient demographics, histopathological types, and prognosis of different molecular subtypes were analysed and compared respectively. Results: MRS and MR imaging features differed from different individuals, but without statistical significance that involves acquiring non-quantitative MR imaging features and NAA/Cr, Cho/Cr, Lip/Cr, Glu and Gln/Cr ratio, to be used to determine molecular subtypes. There was no significant difference of the three molecular subtypes in age, gender and pathological type. The 5-year event-free survival (EFS) of SHH, WNT and non SHH/WNT subtype respectively were 75%, 57.1%, 38.1%, with no significant difference (p = 0.382). 5-year EFS of non SHH/WNT subtype was significantly higher in ≤3 years old group than >3 years old group (p = 0.047). Conclusion: MRS and MR imaging features can’t be used to determine molecular subtypes based on our small sa

关键词： Medulloblastoma molecular subtypes MRS 5-Year EFS

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Analysis of the relevance between molecular subtypes and efficacy of neoadjuvant chemotherapy in breast cancer as well as its prognostic factors

Analysis of the relevance between molecular subtypes and eff...

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2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青...

作者： Fang Li Yueping Liu Department of pathology Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital

Background: Accurate pathological assessment of breast specimens after NACT is crucial. So we should explore the relevance between molecular subtypes and efficacy of neoadjuvant chemotherapy in breast cancer as well as its prognostic factors, which about survival analysis and disease free survival involed, which was one part of contibuting for evaluating in terms of global survival and disease free survival. Methods: 264 patients with breast cancer who received neoadjuvant chemotherapy before surgery in Breast Center, the Fourth Hospital of Hebei Medical University, between January 2007 and May 2011. The relationship between molecular subtypes and neoadjuvant chemotherapy, and clinical pathological features were analyzed. Results: The total pCR rate was 12.50%（33/264）. The pCR rate were 3.03%（1/33）, 9.40%（14/149）, 17.39%（8/46）, 27.78%（10/36） in the subtype of Luminal A, Luminal B, HER2, and Basal-like, respectively. And that had predicted The pCR rate associated with breast cancer molecular subtypes,（P＜0.05）. The pCR rate of Basal-like subtype was highest, HER2 subtype was higher than Luminal A and Luminal B. Multiple factors analysis results showed that: the independent impact factors of 5-year overall survival rate in neoadjuvant chemotherapy breast cancer patients were clinical stage, tumor size, chemotherapy regimens, lymph node metastasis, ER status and pathological remission;the independent impact factors of 5-year disease free survival rate were tumor size, chemotherapy regimens, lymph node metastasis, ER status, PR status and pathological remission（P＜0.05）. Basal-like subtype breast cancer had shorter overall survival and diseasefree survival（P＜0.05）. Conclusions: The pCR rate was frequently observed in HER2 and Basal-like subtypes breast cancer. That could achieve a higher rate of pCR on（ AC→TH） Chemotherapy. But Basal-like subtype breast cancer were showed worse prognosis, due to residual tumor after neoadjuvant chemotherapy, which could be in combination

关键词： breast cancer molecular subtypes neoadjuvant chemotherapy efficacy prognostic

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IMAGGS: a radiogenomic framework for identifying multi-way associations in breast cancer subtypes

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Journal of Genetics and Genomics 2024年第4期51卷 443-453页

作者： Shuyu Liang Sicheng Xu Shichong Zhou Cai Chang Zhiming Shao Yuanyuan Wang Sheng Chen Yunxia Huang Yi Guo Department of Electronic Engineering School of Information Science and TechnologyFudan UniversityShanghai 200433China The Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention(MICCAI)of Shanghai Shanghai 200032China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200433China Department of Ultrasound Fudan University Shanghai Cancer CenterDepartment of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032China Department of Breast Surgery Fudan University Shanghai Cancer CenterDepartment of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032China

Investigating correlations between radiomic and genomic profiling in breast cancer(BC)molecular subtypes is crucial for understanding disease mechanisms and providing personalized *** present a well-designed radiogenomic framework image–gene–gene set(IMAGGS),which detects multi-way associations in BC subtypes by integrating radiomic and genomic *** dataset consists of 721 patients,each of whom has 12 ultrasound(US)images captured from different angles and gene mutation *** better characterize tumor traits,12 multi-angle US images are fused using two distinct ***,we analyze complex many-to-many associations between phenotypic and genotypic features using a machine learning algorithm,deviating from the prevalent one-to-one relationship pattern observed in previous *** radiomic and genomic features are screened using these *** addition,gene set enrichment analysis is performed to investigate the joint effects of gene sets and delve deeper into the biological functions of BC *** further validate the feasibility of IMAGGS in a glioblastoma multiforme dataset to demonstrate the scalability of IMAGGS across different modalities and *** together,IMAGGS provides a comprehensive characterization for diseases by associating imaging,genes,and gene sets,paving the way for biological interpretation of radiomics and development of targeted therapy.

关键词： IMAGGS Radiogenomic framework "lmage-gene-geneset"associations molecular subtypes Breast cancer

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Oncology Research 2023年第5期31卷 697-714页

作者： XUEFENG WANG SICONG JIANG XINHONG ZHOU XIAOFENG WANG LAN LI JIANJUN TANG Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Nanchang UniversityNational Regional Center for Respiratory MedicineNanchang330006China Division of Thoracic and Endocrine Surgery University Hospitals and University of GenevaGenevaSwitzerland Department of Hepatobiliary Surgery Xiantao First People’s Hospital of Yangtze UniversityXiantao433099China Department of Gastrointestinal Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhou510062China Department of Radiation Oncology The Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer HospitalKunming650118China

Pancreatic cancer is associated with high mortality and is one of the most aggressive of malignancies,but studies have not fully evaluated its molecular subtypes,prognosis and response to immunotherapy of different *** purpose of this study was to explore the molecular subtypes and the key genes associated with the prognosis of pancreas cancer patients and study the clinical phenotype,prognosis and response to immunotherapy using single-cell seq data and bulk RNA seq data,and data retrieved from GEO and TCGA ***:Single-cell seq data and bioinformatics methods were used in this *** cancer data were retrieved from GEO and TCGA databases,the molecular subtypes of pancreatic cancer were determined using the six cGAS-STING related pathways,and the clinical phenotype,mutation,immunological characteristics and pathways related to pancreatic cancer were ***:Pancreatic cancer was classified into 3 molecular subtypes,and survival analysis revealed that patients in Cluster3(C3)had the worst prognosis,whereas Cluster1(C1)had the best *** clinical phenotype and gene mutation were statistically different among the three molecular *** of immunotherapy response revealed that most immune checkpoint genes were differentially expressed in the three subtypes.A lower risk of immune escape was observed in Cluster1(C1),indicating higher sensitivity to immunotherapeutic drugs and subjects in this Cluster are more likely to benefit from *** pathways related to pancreatic cancer were differentially enriched among the three *** genes,namely SFRP1,GIPR,EMP1,COL17A and CXCL11 were selected to construct a prognostic ***:Single-cell seq data were to classify pancreatic cancer into three molecular subtypes based on differences in clinical phenotype,mutation,immune characteristics and differentially enriched *** prognosis-related genes were identified for prediction of survi

关键词： Pancreatic cancer molecular subtypes Single-cell sequencing Immune microenvironment Tumor immunity

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The era of personalized treatments:Updates on immunotherapy within urothelial of bladder cancer

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Current Urology 2022年第3期16卷 117-120页

作者： Zhang-Song Wu Song Wu Medical College Shenzhen UniversityShenzhenChina The Huanan Affiliated Hospital of Shenzhen University Shenzhen UniversityShenzhen518000China School of Life Sciences Chinese University of Hong Kong(Shenzhen)ShenzhenChina

Bladder cancer is a complex disease of the urinary system with high morbidity and ***,the introduction of immunother-apies such as immune checkpoint inhibitors(eg,programmed cell death protein 1/programmed death-ligand 1)has proven to be a re-liable means of improving survival outcomes,including patients with limited response to conventional ***,difficult questions remain in clinical practice,such as how to select appropriate patients for personalized treatment,how to predict and assess therapeutic efficacy in advance,and how to enhance the therapeutic benefits of immunotherapy *** issues require urgent ***,we describe recent clinical applications of immune checkpoint inhibitors in bladder cancer therapy,examine underlying mechanisms for treatment failure in a subset of patients,and discuss potential approaches to improve their therapeutic effects.

关键词： Bladder cancer Combination strategies Immune checkpoint inhibitors molecular subtypes Predictive biomarkers

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